Maintaining energy homeostasis requires a balance between energy consumption and energy expenditure. In Western societies, excess food consumption has led to a shift in energy balance resulting in a dramatic increase in obesity (Van et al., (2006) Nature 444, 875-880), a multi-organ disorder that enhances the risk of type 2 diabetes (T2D), hypertension, hyperlipidemia and cardiovascular disease (Mathieu et al., (2008) The International Journal of Biochemistry & Cell Biology 40, 821-836). Impaired metabolism of energy-providing substrates and myocardial lipid accumulation are early abnormalities found in obese and insulin-resistant individuals (Harmancey et al., (2008) Hypertension 5, 181-187). Mitochondrial dysfunction in metabolically active tissues (e.g. adipose, liver and skeletal muscle) is commonly associated with metabolic diseases including metabolic syndrome (MS), insulin resistance (IR) and T2D (Muoio and Newgard, (2008) Nat Rev Mol Cell Biol, 2008. 9, 193-205).
Accordingly, there is a growing need to identify effective therapies to treat and prevent obesity and related metabolic diseases, such as by enhancing mitochondrial function.